Chlorination process

ABSTRACT

A process for the selective chlorination of pyridine, a lower alkyl pyridine or 3-cyanopyridine includes passing the pyridine compound, chlorine and an inert gas through a two stage reaction. In a first reaction zone, these materials are subjected to a hot spot controlled at a temperature of about 350° to about 500° C. The materials are then subsequently passed through a second reaction zone at a relatively lower temperature, for example below about 340° C.

BACKGROUND

The present invention generally relates to a method for selectivelychlorinating pyridine or a substituted pyridine, and more particularlyto such a method conducted in the gas phase in the presence of chlorineas the chlorinating agent.

Chlorinated pyridine derivatives have been prepared by a variety oftechniques. One general approach to preparing chlorinated pyridinesinvolves the chlorination of pyridine or of a pyridine derivative withmolecular chlorine used as the chlorinating agent (Cl₂, hereinafterreferred to as "chlorine"). A number of differing techniques forchlorinating pyridine or its derivatives with chlorine have beendeveloped.

In one facet, thermally-induced chlorinations have been conducted in thevapor phase in a reactor maintained at a generally uniformly hightemperature, generally above 250° C. and even 300° to 400° C., as hasgenerally been described in U.S. Pat. Nos. 2,820,791 and 3,153,044.These methods have in the past presented various disadvantages such aspoor selectivity and substantial formation of tars that clog the reactoror associated pipes, making a continuous operation difficult.

Another chlorination route involves reactions that are initiated bymeans of light or ultra-violet rays. Such methods have been described,for example, in U.S. Pat. Nos. 3,297,556 and 4,054,499. These methods,although they can be operated at temperatures lower thanthermally-induced methods, have lead to the deleterious formation oftarry by-products that foul the light tubes and give rise to acorresponding reduction in the initiation radiation, and hence in theefficiency of the overall reaction or process.

Still other chlorination routes involve the use of chemical compoundsthat initiate the chlorination reaction, either in liquid or in vaporphase. While providing enhanced selectivities, particularly in the gasphase, these routes nevertheless require the use of the chemicalinitiators to achieve acceptable process results.

In light of this background, there remains a need and demand forprocesses for the chlorination of pyridine or substituted pyridineswhich provide high selectivities and acceptable yields and conversions.The present invention addresses this need.

SUMMARY OF THE INVENTION

The present invention relates to the applicant's discovery that thecontrolled generation of an isolated hot spot within a chlorinationreaction zone of generally lower temperature surprisingly leads tounexpected increases in the selectivity of the chlorination of pyridineor substituted pyridines. Thus, one preferred embodiment of theinvention provides a process for selectively chlorinating pyridine or alower alkyl pyridine. A second preferred embodiment comprises a processfor selectively chlorinating 3-cyanopyridine.

The inventive process for such embodiments includes the step of passinga vaporized feed stream including pyridine, a lower alkyl pyridine or3-cyanopyridine, chlorine and an inert gas into a first reaction zonehaving a hot spot controlled at a temperature of about 350° C. to about500° C., and subsequently through a second reaction zone at atemperature below about 340° C. Surprisingly, by this method,chlorination processes of highly improved selectivity are obtained, forexample as compared to similar chlorinations conducted in a reactorhaving a single controlled temperature reaction zone. Additionally, goodyields and conversions are obtained by the process, with significantlyless tarring than would be obtained using a single reaction zoneentirely maintained at the hot spot temperature. As further advantages,the reaction can conveniently be conducted in a tubular reactor,preferably vertically oriented with the reactant feed into the top ofthe reactor. Moreover, the high selectivities are achieved without theneed for using chemical additives for initiation of the reaction as insome prior processes.

These and other objects, advantages and features of the invention willbe apparent upon reviewing the following description and the appendedclaims.

DESCRIPTION OF THE PREFERRED EMBODIMENT

For the purpose of promoting an understanding of the principles of theinvention, reference will now be made to certain embodiments andspecific language will be used to describe the same. It willnevertheless be understood that no limitation of the scope of theinvention is thereby intended, such alterations, further modificationsand applications of the principles of the invention illustrated hereinbeing contemplated as would normally occur to one skilled in the art towhich the invention relates.

As indicated above, one preferred embodiment of this invention relatesto a process for selectively chlorinating pyridine or a lower alkylpyridine. In this regard, as used herein, the term "lower alkyl" means abranched or unbranched alkyl group having from 1 to about 5 carbonatoms, e.g. methyl, ethyl, propyl, isopropyl, butyl, isobutyl, etc.Particularly preferred chlorinations of this embodiment provide for thechlorination of pyridine to form 2-chloropyridine, and the chlorinationof 2-picoline and 3-picoline to form predominantly their corresponding(2- or 3-) chloromethylpyridines and (2- or 3-)dichloromethylpyridines.

As also indicated above, a second preferred embodiment of this inventionrelates to a process for selectively chlorinating 3-cyanopyridine whichis known to yield the isomer products 2-chloro-3-cyanopyridine and2-chloro-5-cyanopyridine (hereinafter referred to as the "2,3-" and"2,5-" isomers, respectively). Particularly notable in this embodimentis the unexpected preference for the selective production in high yieldsof the 2,5-isomer product of the reaction. This result is contrary toother known processes of this kind, and is desirable in that the2,5-isomer cam be readily isolated and has valuable end uses andintermediate uses in industry.

In conducting processes according to the present invention, the chlorineand the pyridine, alkyl pyridine or 3-cyanopyridine, which may be ofsynthetic or natural origin, are usually included in the reactant feedin molar ratios of about 0.1 to about 20 moles of chlorine per mole orpyridine compound. This ratio depends in particular on the number ofhydrogen atoms that are to be substituted with chlorine in the processat hand. More preferably, this ratio ranges between about 0.2 and about15 moles, and most preferably between about 0.3 and about 10 moles ofchlorine per mole of pyridine compound. In the preferred selectiveproduction of 2-chloropyridine by chlorination of pyridine, this molarratio advantageously lies between about 0.2 moles and about 2 moles ofchlorine per mole of pyridine. When chlorinating a lower alkyl pyridineby the inventive process, the preferred ratio lies between about 2 andabout 20 moles of chlorine per mole of alkyl pyridine involved in thereaction. With the 3-cyanopyridine embodiment, this preferred ratio liesbetween about 0.5 and about 2.0 moles of chlorine per mole of startingmaterial involved in the reaction.

Aside from the reactants mentioned above, it is advantageous to makeuse, in the method according to the invention, of inert gas additivessuch as water vapor, nitrogen and/or other inert gases which do notparticipate in the chlorination reaction. Highly desirable chlorinationreactions are conducted in the presence of water vapor provided at alevel of about 0.1 to about 25 moles per mole of pyridine compoundinvolved. More preferably, water vapor quantities of about I to about 15moles per mole of pyridine compound are employed. Although the watervapor or other inert gas may be provided to the reactor in any suitablefashion, water vapor is advantageously supplied by premixing water andthe pyridine compound involved, passing this mixture into an evaporator,and then passing the vapors thus obtained into the chlorination reactionzone.

As will be readily understood and appreciated by those experienced inthe field, it may also be desirable in some instances to conduct thechlorination reaction in the presence of additives acting as dilutents,but inert with respect to the chlorination reaction. These dilutents areincluded in order to minimize the superheating of the reaction mixtureand to avoid the condensation of reaction products of low volatility.Suitable such additives include chlorine-containing derivatives ofaliphatic compounds such as carbon tetrachloride or inorganic productssuch as hydrogen chloride or nitrogen, although many others will also beacceptable and used by practiced artisans without need for resort to anyundue experimentation.

In the process of the invention, a vaporized feed stream including thepyridine compound, chlorine and inert gas is passed into a firstreaction zone that includes a hot spot controlled at a temperature ofabout 350° C. to about 500° C. This hot spot may be thermally produced,for example, by communicating heat into the reaction zone by a heatsource exterior of the reactor. More preferably in the presentinvention, the hot spot is controlled at a temperature of about 360° toabout 470° C., and most preferably about 360° C. to about 420° C. Thehot spot of most advantageous temperature for a particular reaction willdepend upon several factors such as the specific reactants and inertdilutents involved, the flow rate of materials through the hot spot, andthe like. Controlling and accounting for these and similar parameters inachieving most beneficial hot spot temperatures will readily beaccomplished by those who work in the area.

Subsequent to contacting the feed stream materials with the hot spotreaction zone, the materials are passed into a second reaction zone at atemperature relatively lower than that of the hot spot. For example,this second reaction zone temperature in the applicant's work thus farhas advantageously been below about 340° C., preferably in the range ofabout 100° C. to about 340° C., and more preferably in the range ofabout 200° to about 340° C. Again, selection and use of most beneficialtemperatures in this second reaction zone will pose no undue burden uponthe skilled artisan.

It is preferred that the feed stream residence time in the hot spotreaction zone be shorter than its residence time in the second,lower-temperature reaction zone. For example, residence times of about 2seconds or less are desirable in the hot spot reaction zone, whileresidence times in the second reaction zone may be longer, for instanceseveral minutes, but are usually up to about 30 seconds, preferablyabout 5 to about 10 seconds.

After the chlorination is complete, the chlorinated product or productscan be recovered and isolated in a conventional fashion. For example,the crude reaction product can be treated with a basic material andextracted, for instance with chloroform or another similar extractingagent. Further purification and recovery steps, e.g. distillation, etc.will be conventionally employed if desired.

The chlorinated pyridine products obtained by the process of the presentinvention are suitably employed as chemical intermediates in themanufacture, for example, of products used in agriculture, cosmetics andthe pharmaceutical industry.

For the purposes of promoting a further understanding of the presentinvention and its preferred features and embodiments, the followingexamples are being provided. It will be understood, however, that theseexamples are illustrative, and not limiting, in nature.

EXAMPLES 1-11 Chlorinations of Pyridine

A chlorination reactor for use in the present invention was constructedas follows. A quartz tube having a length of 45 cm and a diameter of 2cm was vertically oriented. Above and directly connected to the tube wasa feed mixing manifold constructed of PYREX. The feed mixing manifoldcontained a central thermowell inlet, two gas feed ports and a liquidfeed nozzle. Nitrogen gas and chlorine gas, and all liquid feed to thereactor could be fed separately and independently of each other.Preheating was provided in the manifold by an external heat source. Inall runs, the preheated area was maintained between about 100° C. and200° C.

A hot spot was created at the top of the quartz tube by means of beadedheat tape. The hot spot length on the tube was from about 2 to 4 cm. Theremainder of the tube was heated with a tube oven. A receiver wasconnected at the bottom of the reactor tube. Materials were fed to themanifold at a rate that gave residence times between 6 and 9 secondsthrough the entire 45 cm tube. The molar ratio of chlorine to pyridinewas 1-2:1 and for water to pyridine it was 8:1.

For product analysis, the crude acidic mixture exiting the reactor wascollected in the receiver at the hot tom of the reactor tube. The crudematerial was made basic and extracted with chloroform. GC analysis ofthe combined organic extract gave the weight percent of each component.

Eleven chlorination runs were conducted under varying temperatureconditions in the two reaction zones of the reactor. Also, varyingpyridine sources were employed. After analysis of the product, theconversion of pyridine, yield of 2-chloropyridine and2,6-dichloropyridine, and the selectivities for these two chlorinatedproducts were determined. The results are set forth in Table 1 below, inwhich the designation "NA" means not assayed.

                                      TABLE 1                                     __________________________________________________________________________       Temp. (°C.)                                                                   Temp. (°C.) Yield (%)                                                                           Yield (%)                                                                           Select (%)                                                                          Select (%)                        Hot Spot                                                                             Second Pyridine    2-Cl  2,6-diCl                                                                            2-Cl  2,6-diCl                       Ex.                                                                              Zone   Zone   Source                                                                              Conversion                                                                          Pyr   Pyr   Pyr   Pyr                            __________________________________________________________________________     1 168    224    .sup. Spec.sup.a                                                                     3.1   5.3  0.1   NA    1.8                             2 220    240    Spec  0      7.0  0.1   NA    NA                              3 283    248    Spec   9.8  13.7  0.5   NA    5.3                             4 357    130    .sup. 1 degree.sup.b                                                                25.2  18.4  0.7   73.2  3.0                             5 367    335    1 degree                                                                            33.5  34.4  1.8   102.4 5.4                             6 393    169    1 degree                                                                            41.9  27.3  1.3   65.2  3.2                             7 393    269    Spec  32.5  29.7  1.0   91.5  3.1                             8 396    190    Spec  49.1  31.9  1.5   65.0  3.1                             9 397    271    Spec  31.5  32.0  1.5   101.6 4.8                            10 469    290    Spec  57.1  41.7  2.4   72.9  4.1                            11 589    188    Spec  56.1  11.6  0.8   20.6  1.4                            __________________________________________________________________________     .sup.a "Spec" = Spec. grade pyridine as available from Reilly Industries,     Inc, Indianapolis, Indiana.                                                   .sup.b "1 degree" = pyridine distilling within 1 degree, commercially         available from Reilly Industries, Inc.                                   

As the data in Table 1 shows, a hot spot reaction zone can beadvantageously employed to achieve high selectivity for 2-chloropyridinewith good yields and conversions in the applicant's work, theadvantageous results were obtained using a hot spot of about 350° C. toabout 500° C. At temperatures substantially above 500° C., e.g. in run11 with a hot spot of 589° C., conversions of pyridine are high;however, yields of and selectivities for 2-chloropyridine are very low.On the other hand, using hot spot temperatures substantially below about360° C., e.g. as in runs 1, 2 and 3 in which respective hot spottemperatures of 283° C., 220° C. and 168° C. were used, conversions arevery poor as are yields of 2-chloropyridine. In contrast, in runs inwhich a hot spot temperature between about 350° C. and about 500° C.were used, conversions were good, yields of 2-chloropyridine were good,and selectivities for 2-chloropyridine were good. For instance, inExamples 5, 6, 7 and 9, in which the hot spot temperature ranged betweenabout 360° C. mid about 400° C., conversions ranged between 30 percentand 42 percent, while selectivities for 2-chloropyridine were between 90percent and 100 percent. This advantageous combination ofconversions/yields/selectivities for 2 -chloropyridine is highlyunexpected and highlights the dramatic nature of the applicant'sdiscovery.

While some material balance inconsistencies exist in some or thereported runs, they are minor. These inconsistencies are based uponslight experimental and analytical errors inherent in the system, andthe reported runs nevertheless represent solid and reproducible examplesof processes of the invention.

EXAMPLES 12-13 Chlorinations of 3-Picoline

3-Picoline was chlorinated with (Example 12) and without (Example 13)the use of a hot spot as in the invention. Thus, using the reactorpreviously described in connection with Examples 1-11, 3-picoline waschlorinated using a hot spot temperature of 350° C., and a secondreaction zone temperature of 200° C. For this run, the molar feed ratioof chlorine to 3-picoline was 7.4, and this ratio of water to 3-picolinewas 8.0. Total residence time in the reactor was 6.1 seconds. Thepredominant products were 3-chloromethylpyridine and3-dichloromethylpyridine, which were recovered in respective yields of17.9 percent and 12.1 percent. The conversion of 3-picoline in this runwas 90%. In another run, 3-picoline was chlorinated employing a "hotspot" temperature of 200° C. and a second reaction zone temperature of200° C. The molar feed ratio of chlorine to 3-picoline was 8.1, and theratio of water to 3-picoline was 8.0. Total residence time in thereactor was 6.3 seconds. In this rim, conversion of 3-picoline was only61 percent and the predominant product was 3-chloromethylpyridine, whichwas recovered in 19.1 percent yield. These runs demonstrate that a hotspot as used in the present invention provides superior conversion whileyielding predominantly both 3-chloromethylpyridine and3-dichloromethylpyridine.

EXAMPLE 14-15 Chlorinations of 2-Picoline

Using the above-described reactor, 2-picoline was chlorinated with(Example 14) and without (Example 15) the use of a hot spot as providedby the present invention. Thus, in one rim, 2-picoline was chlorinatedusing a hot spot temperature of 350° C. and a second reaction zonetemperature of 200° C. The molar ratio of chlorine to 2-picoline was7.5, and the molar ratio of water to 2-picoline was 8.1. Residence time(total) in the reactor was 6.5 seconds. Similar to Examples 12, thepredominant products were the corresponding chloromethylpyridine anddichloromethylpyridine, i.e. 2-chloromethylpyridine and2-dichloromethylpyridine (representing 15.3 and 10.7 GC area % of theproducts, respectively). In another run (Example 15), 2-picoline waschlorinated without using a hot spot as in the invention. Thus,2-picoline was chlorinated using a "hot spot" temperature of 200° C.,and a second reaction zone temperature of 200° C. The molar ratios ofchlorine to 2-picoline and water to 2-picoline were 7.0 and 8.0,respectively. Total residence time in the reactor was 7.1 seconds.Again, conversion was significantly reduced as compared to thecorresponding hot spot run. The predominant product was2-chloromethylpyridine, which registered 11.9 GC area %. 2-Picoline and2-dichloromethylpyridine registered at 13.6 and 3.3 GC area %,respectively.

EXAMPLE 16-20 Chlorinations of 3-Cyanopyridine

Using the reactor construction and general procedure previouslydescribed in connection with Examples 1-11, seven chlorination runs wereconducted using a 3-cyanopyridine source under varying temperatureconditions in the reaction zones of the reactor. The molar ratio ofchlorine to the 3-cyanopyridine starting material was 1.0:1, and forwater to the pyridine source was 3.0:1. The feed rate for the materialsto the manifold was selected to give residence times between 6 and 9seconds similar to that used in Examples 1-11.

For purposes of analysis, the crude product mixture exiting the reactorwas collected in the receiver at the bottom of the tube. This materialwas then neutralized to pH about 7 in the aqueous phase. Layers wereseparated and the crude organic phase analyzed. GC analysis of thecombined organic extract from the reaction gave the weight percentage ofeach component. The conversion of original 3-cyanopyridine, the yieldsof both predominant 2,3- and 2,5-isomers, and the selectivities for eachwere then determined. The results of this analysis are set forth inTable 2 below.

                                      TABLE II                                    __________________________________________________________________________       Temp. (°C.)                                                                   Temp. (°C.)                                                     Hot Spot                                                                             Second Pyridine   Yield (%)                                                                           Yield (%)                                                                           Select (%)                                                                          Select (%)                      Ex.                                                                              Zone   Zone   Source                                                                             Conversion                                                                          2,5-  2,3-  2,5-  2,3-                            __________________________________________________________________________    16 300    300    3-CN 69    22     1    32    <1                              17 342    218    3-CN 21     3    <1    14     5                              18 384    242    3-CN 46    39     8    84    17                              19 412    265    3-CN 73    61    10    84    14                              20 443    287    3-CN 79    67    12    85    15                              21 490    320    3-CN 77    59    14    77    18                              22 556    202    3-CN 74    54    11    73    15                              __________________________________________________________________________

As evidenced in the data in Table II, the hot spot reaction zone ofapplicant's preferred embodiment is advantageous in several unexpectedways in connection with the chlorination of 3-cyanopyridine. With notemperature zone variation or with only a minor hot spot zone as shownin Examples 16 and 17, respectively, while both 2,3- and 2,5-isomers areproduced, the conversions were erratic and the selectivities for thepreferred 2,5-isomer were low. In contrast, when the hot spot zone waselevated to temperatures within the preferred range of about 350° C. toabout 500° C. and with the second zone lowered to below the preferredabout 340° C. temperature, unexpected and advantageous results wereobtained as reported in Examples 18-22 in Table II. For example, overallconversions were consistently high and even in the instance of Example18 where a lower conversion was shown for some reason, the yields ofboth isomers and in particular the preferred 2,5-isomer weresubstantially increased. As further evidence of the unexpected nature ofthis result, the selectivity of the reaction to produce this 2,5-isomerwas also dramatically higher in these same Examples 18-22. The reportedruns are clear evidence of the advantageous combination of highconversions/yields/selectivities for 2-chloro-5-cyanopyridine which ishighly unexpected and supports the significance of applicant'sdiscovery.

While the invention has been illustrated and described in detail in theforegoing description, the same is to be considered as illustrative andnot restrictive in character, it being understood that only thepreferred embodiment has been described and that all changes andmodifications that come within the spirit of the invention are desiredto be protected.

What I claim is:
 1. A process for selectively chlorinating3-cyanopyridine, comprising:passing a vaporized reed stream including3-cyanopyridine, chlorine and an inert gas into a first reaction zonehaving a hot spot controlled at a temperature of at about 350° C. toabout 500° C., and subsequently through a second reaction zone at atemperature below about 340° C.
 2. The process or claim 1 wherein thefirst reaction zone has a hot spot controlled at a temperature of about360° C. to about 470° C.
 3. The process of claim 1 wherein the firstreaction zone has a hot spot controlled at a temperature of about 360°C. to about 420° C.
 4. Thee process of claim 1 wherein the secondreaction zone is at a temperature above about 100° C.
 5. The process ofclaim I wherein the second reaction zone is at a temperature above about200° C.
 6. The process of claim 5 wherein the second reaction zone is ata temperature above about 100° C.
 7. The process of claim 5 wherein thesecond reaction zone is at a temperature above about 200° C.
 8. Theprocess of claim 1 wherein the inert gas is water vapor.
 9. The processof claim 8 wherein the inert gas is water vapor.
 10. The process ofclaim 9 wherein the feed stream includes 3-cyanopyridine so as toproduce 2-chloro-5-cyanopyridine.
 11. A process for producing2-chloro-5-cyanopyridine by chlorination of 3-cyanopyridine withchlorine, comprising:passing a vaporized feed stream including3-cyanopyridine, chlorine and an inert gas into a first reaction zonehaving a hot spot at a temperature of about 350° C. to about 420° C.,and subsequently passing the stream through a second reaction zonehaving a temperature of about 200° C. to about 340° C., so as to produce2-chloro-5-cyanopyridine.
 12. The process of claim 11 wherein theresidence time of said feed stream in said first reaction zone is about2 seconds or less.
 13. The process of claim 11 wherein said residencetime is about 1 second or less.
 14. The process of claim 11 wherein saidinert gas is water vapor.
 15. The process of claim 11 wherein the molarratio of chlorine to 3-cyanopyridine in said feed stream is about 0.2:1to 2.0:1.
 16. The process of claim 15 wherein said molar ratio is about0.5:1 tp 1.5:1.
 17. A process for selectively chlorinating pyridine, alower alkyl pyridine or 3-cyanopyridine, comprising:passing a vaporizedfeed stream including pyridine, or lower alkyl pyridine or3-cyanopyridine, chlorine and an inert gas into a first reaction zonehaving a hot spot controlled at a temperature of at about 350° C. toabout 500° C., and subsequently through a second reaction zone at atemperature below about 340° C.
 18. The process of claim 17 wherein thevaporized feed stream includes 3 -cyanopyridine.
 19. The process ofclaim 17 wherein the first reaction zone has a hot spot controlled at atemperature of about 360° C. to about 470° C.
 20. The process of claim17 wherein the first reaction zone has a hot spot controlled at atemperature of about 360° C. to about 420° C.
 21. The process of claim17 wherein the second reaction zone is at a temperature above about 100°C.
 22. The process of claim 17 wherein the second reaction zone is at atemperature above about 200° C.
 23. The process of claim 22 wherein thesecond reaction zone is at a temperature above about 100° C.
 24. Theprocess of claim 22 wherein the second reaction zone is at a temperatureabove about 200° C.
 25. The process of claim 18 wherein the inert gas iswater vapor.
 26. The process of claim 25 wherein the inert gas is watervapor.
 27. The process of claim 26 wherein the feed stream includes3-cyanopyridine so as to produce 2-chloro-5-cyanopyridine.